Siprianus Ugroseno Yudho Bintoro

Kemajuan kedokteran modern telah menghasilkan terapi yang semakin presisi—bedah minimal invasif, kemoterapi, radioterapi, hingga terapi target molekuler. Namun, penyakit kronis seperti kanker dan penyakit jantung tetap meningkat dan kerap mengalami kekambuhan. Buku ini menawarkan perluasan paradigma: penyakit tidak semata dipahami sebagai gangguan seluler, tetapi sebagai indikator gangguan sistemik yang melibatkan regulasi biologis, psikologis, sosial, dan etis. Melalui pendekatan biologi sistem dan integrasi dengan konsep Islam, buku ini memperkenalkan gagasan pembalikan arah karakter sebagai terapi hulu. Karakter dipahami sebagai pola regulasi diri yang memengaruhi lingkungan biologis internal tempat sel hidup. Stres kronis, bahasa destruktif, dan relasi sosial yang rapuh membentuk medan biologis yang tidak stabil. Sebaliknya, regulasi diri, empati, dan orientasi hidup yang terarah memperkuat koherensi sistem tubuh. Buku ini tidak menggantikan terapi medis modern, tetapi melengkapinya melalui pendekatan preventif, kuratif pendamping, dan rehabilitatif yang murah, etis, dan aplikatif. Dengan kerangka non-moralistik dan berbasis sains, buku ini menawarkan sintesis antara iman, sistem biologi, dan praktik klinis untuk membangun paradigma kesehatan yang lebih utuh.

Background: The exploration of simple, cost-effective, and low-risk prognostic markers, such as the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) as predictive factors for survival in diffuse large B-cell lymphoma (DLBCL) patients receiving R-CHOP therapy has become increasingly important due to the variability in results seen in prior studies. Methods: This observational cross-sectional study analyzed NLR, LMR, and PLR as predictors of survival in DLBCL patients treated with R-CHOP. Data was collected from DLBCL patients from June 2017 to June 2022. All statistical analyses were performed using R version 4.2.3 using pROC package for receiver-operating characteristic curves analyses. Univariate and multivariate logistic regression analyses were performed to assess predictors’ association with overall survival (OS). Results: There were 112 DLBCL patients receiving R-CHOP, 87 were classified as surviving, while 25 were not. Univariate logistic regression analyses revealed significant associations between overall survival (OS) and IPI scores (p < 0.001). Conversely, gender, response to R-CHOP therapy, and hematologic indicators of NLR > 2.0, PLR > 213.4, and LMR > 1.1 did not show significant associations with OS. Multivariable logistic regression analysis using backward selection identified LMR (p = 0.036; 0.24 (95%CI: 0.05 to 0.84) as independent predictors for OS in DLBCL patients. Conclusions: Our study revealed several fundamental risk factors, including extranodal involvement, ECOG performance status, LDH, and LMR, were independently associated with 2-year mortality in DLBCL patients before initiating R-CHOP therapy. However, due to the limitations of this study, further research with larger sample sizes is warranted.

Background: Beta thalassemia major is the most common monogenic mutation disorder in Indonesia, with steadily increasing frequency. However, there are limited studies regarding genetic distribution and its relationship with the patient’s clinical manifestation. This study aimed to identify the genetic mutation frequency and its association with the clinical phenotype pattern among β-thalassemia major patients in East Java, Indonesia. Methods: In this observational study, we include subjects who have diagnosed with β-thalassemia previously through Hb electrophoresis. Demographic distribution with several ethnicities of Javanese, Sundanese, Chinese, Maduranese, and Batak was recorded. From each subject, a total of 6 mL of blood sample was collected and divided into two ethylene diamine tetraacetic acid (EDTA) tubes for CBC and DNA extraction. DNA samples were analyzed by PCR and followed by Sanger sequencing. Results: A total of 91 subjects were included in this study, with a median age of 22.25 ± 7.56 years old; consisting of 52 females and 39 males, with Javanese as the most common ethnicity. There are 22 types of mutation were identified through Sanger sequencing. The most common mutation was IVS-1-5/CD 26 and the CD 35/CD 26 observed in 36 (39.5%) and 19 (20.8%), respectively. While 9 subjects (9.8%) had no mutation detected. Several clinical phenotypes, including iron overload, short stature, severe anemia, and splenomegaly, were most prevalent among the two most common genetic mutations. Conclusion: There is variability in clinical phenotype in β-thalassemia observed in several types of genotype mutations. Among all the mutations found in East Java, the genotypes IVS-1-5/CD 26 and CD 35/CD 26 were the two most frequent genotypes. Those genotypes are linear with the severity of the phenotype in β-thalassemia, such as severe anemia, iron overload, short stature, and splenomegaly.

Introduction: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a leading cause of cancer-related mortality worldwide. Despite recent advances in immunotherapy and targeted agents, treatment efficacy is frequently limited by tumor heterogeneity, drug resistance, and systemic toxicity. Natural products, particularly carotenoid-derived compounds, have emerged as promising multi-target anticancer agents. Xanthophylls, a class of oxygenated carotenoids, exhibit pleiotropic biological activities that are relevant to cancer therapy; however, their potential against HCC remains incompletely explored. This study aimed to systematically evaluate the anti-HCC potential of xanthophyll-rich extracts from Garcinia dulcis pulp using integrated metabolomic, in silico, and in vitro approaches. Methods: Xanthophyll-rich extracts from G. dulcis pulp were prepared using microwave-assisted extraction. Phytochemical profiling was performed using UHPLC–ESI–MS/MS. In silico analyses included bioactivity prediction, ADMET profiling, target identification, network pharmacology, pathway enrichment, and molecular docking against key HCC-related proteins (EGFR, BCL-2, and mTOR). In vitro antiproliferative activity was assessed using MTT assays on HepG2 and Huh7 hepatocellular carcinoma cell lines, with THLE-2 normal hepatocytes used as controls. Results: Metabolomic analysis revealed a xanthophyll-dominated profile, with zeaxanthin and lutein as the major constituents, alongside fucoxanthin, astaxanthin, β-cryptoxanthin, β-carotene, and canthaxanthin. In silico predictions demonstrated high antineoplastic and pro-apoptotic activities, with strong involvement in the HIF-1, EGFR, PD-1/PD-L1, JAK–STAT, and mTOR signaling pathways. Molecular docking confirmed stable and high-affinity interactions of xanthophylls with EGFR, BCL-2, and mTOR. In vitro assays showed selective cytotoxicity against HCC cells, with IC₅₀ values of 42.8 ± 3.6 µg/mL (HepG2) and 58.4 ± 4.9 µg/mL (Huh7), while exhibiting significantly lower toxicity toward normal hepatocytes. Conclusions: Xanthophyll-rich extracts from Garcinia dulcis pulp exhibit potent and selective anti-hepatocellular carcinoma activity through multi-target mechanisms involving oncogenic signaling, apoptosis regulation, and tumor metabolism. These findings support the translational potential of G. dulcis xanthophylls as promising natural candidates for further development in HCC therapy.

Introduction: Mounting evidence indicates that the p53 Pro72Arg single-nucleotide polymorphisms (SNPs) may play a role in modulating hepatocarcinogenesis in the setting of chronic HBV infection. However, there is currently a lack of studies focusing on this genetic variant in Indonesia, a country characterized by its diverse genetic landscape comprising over 1300 distinct ethnic groups. We aimed to investigate the association between the p53 Pro72Arg polymorphism and the risk of hepatocellular carcinoma (HCC) among Indonesian patients with chronic HBV infection. Methods: A total of 140 patients with chronic hepatitis B (CHB) were recruited, including 79 with HCC and 61 without HCC serving as controls. We used direct sequencing of DNA extracted from peripheral blood to analyze the SNPs of p53 codon 72. Results: The distribution of p53 Pro72Arg genotypes among Indonesian CHB patients was 12.9% for proline homozygotes (Pro/Pro), 31.4% for arginine homozygotes (Arg/Arg), and 55.7% for proline/arginine heterozygotes (Pro/Arg). Despite the lack of association between the SNPs and HCC risk in the overall population, both the Pro/Arg and Arg/Arg genotypes demonstrate an increased susceptibility to HCC compared to Pro/Pro genotypes exclusively in the Madurese ethnic group. Additionally, we discovered that in those with decompensated cirrhosis, the heterozygote Pro/Arg was more likely to develop HCC than the homozygous Pro/Pro. No significant association was found between the SNPs of p53 Pro72Arg and the clinicopathological characteristics of HCC. Conclusions: The p53 Pro72Arg polymorphism might contribute to hepatocarcinogenesis in Indonesian chronic hepatitis B patients, particularly Madurese and those with liver decompensation.

Background/Objectives: Tyrosine kinase inhibitors (TKIs) have transformed the treatment of chronic myeloid leukemia (CML), yet emerging evidence indicates an increased risk of vascular adverse events, particularly peripheral artery disease (PAD). Reliable biomarkers for early detection of TKI-related vascular toxicity are still lacking. Methods: A cross-sectional study was conducted on 78 patients with chronic-phase CML treated at Dr. Soetomo General Hospital, Surabaya. PAD was confirmed using ankle–brachial index. Serum oxidized low-density lipoprotein (OxLDL) and interleukin-10 (IL-10) levels were measured using ELISA. Results: PAD was detected in 20% of subjects. The PAD group showed significantly higher OxLDL, lower IL-10, and a markedly elevated OxLDL/IL-10 ratio (all p < 0.001). OxLDL remained independently associated with PAD after adjustment (adjusted OR = 1.132, 95% CI 1.020–1.255, p = 0.019). OxLDL/IL-10 ratio yielded a good diagnostic value (sensitivity 87.5% and specificity of 88.7%). Conclusions: Elevated OxLDL and an increased OxLDL/IL-10 ratio are associated with PAD in CML patients receiving TKI therapy and demonstrated a good diagnostic performance for early detection of TKI-induced vascular toxicity.

The high morbidity and mortality rates due to pneumonia in developing countries indicate that a more affordable marker is needed to determine the degree of inflammation in cases of pneumonia infection. The neutrophil-to-lymphocyte ratio (NLR) is a simple indicator used extensively in evaluating the systemic inflammatory response. An observational cross-sectional study of 297 pneumonia patients was conducted using medical records as the source document. The patients’ blood was taken during the hospital admission to obtain neutrophil and lymphocyte values. Meanwhile, the PSI score was used during the hospital admission to assess the severity of the pneumonia. Bivariate analysis using Spearman correlation was used to determine the correlation between NLR and pneumonia severity. The ROC curve was used to determine the cut-off value of NLR to distinguish mild from severe patients. The results of the Spearman correlation test analysis showed that the correlation between the NLR and the pneumonia severity was significantly positive (r = 0.130; p = 0.025). Furthermore, the median NLR value was higher in patients with severe pneumonia than in those with milder pneumonia severity (13.01 vs. 11.79 vs. 6.75). The NLR cut-off value of 9.07 was obtained to differentiate patients with mild severity and those with more severe disease. In conclusion, there is a correlation between the neutrophil-to-lymphocyte ratio and the severity of patients’ pneumonia.

Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells and the excessive accumulation of monoclonal protein. While primary manifestations such as bone pain, renal dysfunction, anemia are well-documented features, extra-hematological complications, including achalasia, are exceedingly rare. We present a 76-year-old male with 10-month history of persistent dysphagia. Laboratory test revealed anemia, leukocytosis, and neutrophilia, while serum protein electrophoresis indicated dysproteinemia. Bone marrow aspiration confirmed MM with 25% plasma cell infiltration. Imaging and endoscopic findings further identified a lytic cervical spine lesion and esophageal motility dysfunction consistent with achalasia. This case presents a rare presentation extra-hematological presentation of MM, emphasizing the need for a comprehensive diagnostic approach to facilitate timely recognition and appropriate management of MM.

Next-generation sequencing (NGS) has emerged as a powerful tool for advancing research in chronic myeloid leukemia (CML) by providing a deeper understanding of its genetic complexity. Beyond detecting the hallmark BCR::ABL1 fusion gene, NGS has enabled the identification of additional mutations associated with disease progression, therapy resistance, and clonal evolution. NGS also facilitates the detection of rare BCR::ABL1 fusion variants and cryptic rearrangements, offering a more refined genetic characterization of the disease. Additionally, it enhances the study of minimal residual disease (MRD) and evolving resistance patterns, which are crucial for developing targeted therapeutic strategies. However, challenges such as data interpretation, standardization, and cost constraints continue to limit the widespread application of NGS in routine research and clinical settings. This review explores the contributions of NGS to CML research, highlighting its role in uncovering novel genetic alterations, tracking clonal evolution, and identifying potential therapeutic targets. As sequencing technologies evolve, NGS is expected to further shape the future of CML research, providing critical insights that may ultimately refine disease management strategies.

Gallbladder adenocarcinoma has a high mortality rate, with approximately 1.7% cancer-related deaths worldwide. Cancerassociated thrombosis (CAT), including deep vein thrombosis (DVT), can significantly increase the risk of mortality within cancer patients, especially in pancreatic, brain, and intra-abdominal cancers, as well as in advanced and metastatic cancers. In this case report, there was a 45-year-old male patient diagnosed with advanced gallbladder adenocarcinoma UICC stage IVB with a TNM stage of T2b, N0, M1 with liver metastases who experienced pain and swelling in both lower limbs after undergoing a VI-A cycle of chemotherapy with gemcitabine capecitabine. The risk of thrombosis was calculated using the modified Khorana-Vienna CAT scores, which increased during every chemotherapy session. In this case, the Khorana-Vienna CAT score was calculated during two latest cycle of chemotherapy that somewhat considered delayed as the patient had already shown hypercoagulopathy symptoms and developed a poorer prognosis. Early CAT scoring, ideally before starting chemotherapy session, potentially improves thrombosis prognosis. The patient's condition improved after administration of antithrombotic agents. Chemotherapy agents and other factors, including the cancer site and presence of metastatic cancer, influence the risk of CAT. Risk predictor scores are required to assess the risk of CAT and benefits of prophylactic treatment. Prophylactic therapy can be initiated in patients with high-risk CAT, calculated using the modified Khorana and Vienna CAT scores, to prevent thrombosis and improve patient outcomes.